The overall objective of this project is to determine how herpes simplex virus (HSV) persists in cells which are either latently infected or which have become morphologically transformed as a consequence of an initial interaction. Specifically we wish to define which sequences of HSV-2 DNA code for products which are sufficient to alter the phenotype of cells; determine the arrangement of the viral sequences which are retained; and analyze the viral gene products. One region of the HSV-2 genome defined by the Bg1II N fragment (0.58-0.62 map units) has been used to transform primary and established lines of rodent cells. The transformants show altered growth properties, are tumorigenic, and retain viral DNA. The complement of proteins encoded by the Bg1II N sequences have been defined by selection hybridization and in vitro translation. Experiments to more precisely define the transforming genes within Bg1II N and to determine whether other regions of the HSV-2 genome have transforming potential are in progress. Additionally, we would like to determine whether expression of particular viral functions is necessary to maintain the HSV genome in a latent state in neurons. In situ hybridization to human and animal sensory ganglia with defined fragments of the viral genome are providing information toward understanding the state of the virus in a latent infection.